Contraction -induced injury of weight -bearing muscles and the role of reactive oxygen species.

Abstract

For small, non-weight bearing muscles of old mice, severe contraction-induced injury causes a permanent 20% reduction in mass and maximum force. With aging, large, weight-bearing muscles appear to lose mass and force more rapidly than small, non-weight-bearing muscles, yet recovery of large, weight-bearing muscles following contraction-induced injury has not been investigated. The hypothesis is tested that two months following a severe contraction-induced injury to large, weight-bearing muscles, muscles of adult mice recover, whereas those of old mice sustain permanent deficits in mass and force. For muscles of adult mice, those of male mice regained control values, while muscles of female mice sustained reductions of 9% in mass and 16% in force. For muscles of old mice, those of male mice sustained decreases of 24% in mass and 32% in force, while corresponding deficits of 14% and 40% remained for muscles of female mice. The conclusion is that a severe contraction-induced injury to large, weight-bearing muscles of old animals causes irreversible damage. Contraction-induced injury consists of an initial disruption to individual sarcomeres followed by sealing off of the focal damage and a more severe secondary injury from reactive oxygen species (ROS) released by invading inflammatory cells. The location and timing of the release of ROS relative to the sealing off process is not well documented. The hypothesis is tested that daily treatment of muscles of adult mice with a membrane permeable antioxidant, N-2-mercaptopropionyl-glycine (MPG), attenuates contraction-induced injury. Contrary to the hypothesis, no differences in force deficits were observed between muscles of antioxidant- and saline-treated mice. The results could not rule out the short residence time of MPG as a potential reason for the ineffectiveness. Therefore, the null hypothesis is tested that the continuous overexpression of genes for intracellular antioxidants has no effect on contraction-induced injury. No differences in force deficits were observed among the groups of mice. The ineffectiveness of increasing levels of intracellular antioxidants was consistent with the infiltration of inflammatory cells and release of ROS occurring predominantly at the site of the initial injury after the completion of sealing off.